Contact lens related eye infections impact millions of people yearly. Standard guidelines for lens care can minimize eye infection, but it has been shown that only about 50% of lens wearers adhere to appropriate guidelines. During usual use and storage procedures, microorganisms adhere to contact lenses. Daily lens cleaning removes most of these microorganisms, but sometimes microbes establish biofilms on lenses and often such biofilms are not satisfactorily removed despite disinfection and cleaning with systems currently available. In many cases the source of the microorganisms is the lens case where biofilms have developed. In addition to resistance to lens disinfectant/cleaning systems, biofilms formed by pathogenic organisms are of increasing clinical importance due to their resistance to antibiotics and host immune responses as well as their ability to develop on indwelling medical devices. Nitric oxide (NO) has been shown to efficiently kill bacteria and fungi in the mammalian host by the action of granulocytes that produce NO. We have previously exploited the antimicrobial properties of NO to create slow NO releasing compounds that are capable of killing both fungi and bacteria growing planktonically. In the present investigation, we will test the principle that such compounds are also capable of killing organisms growing in established biofilms. In this context, the aim of this Phase I proposal is to test the hypothesis that NO treatment is capable of killing microbial cells that comprise biofilms formed by causative agents of contact lens related eye infection. The sensitivity of appropriate bacterial, fungal, and mixed species biofilms to NO treatment will be determined. If proof of principle is obtained, the ultimate goal of the investigation to be pursued in Phase II is the development of an appropriate delivery vehicle for lens and lens case sterilization. We will initiate this work during Phase I, and possible approaches are also discussed herein.